p-Toluenesulfonic acid monohydrate → 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 922359ノート

反応式

HRID 922359 の反応式
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[F:15][C:16]1[N:21]=[C:20]([CH:22]=O)[CH:19]=[CH:18][CH:17]=1.OS([O-])=O.[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[F:15][C:16]1[N:21]=[C:20]([C:22]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([O:11][CH3:12])=[CH:8][C:7]=3[O:13][CH3:14])[N:1]=2)[CH:19]=[CH:18][CH:17]=1

参加物

6

反応物 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 106067416-Fluoropyridine-2-carboxaldehydeHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium Bisulfite

生成物 1

HCID 1364081482-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one収率 49%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
120 °C

実験手順

To a solution of 2-amino-4,6-dimethoxybenzamide (0.737 g, 3.76 mmol) and 6-fluoropicolinaldehyde (0.470 g, 3.76 mmol) in N,N-dimethylacetamide (20 mL), NaHSO3 (58.5% SO2 content, 1.0 g, 5.63 mmol) and p-toluenesulfonic acid monohydrate (0.143 g, 0.75 mmol) were added. The reaction was heated at 120° C. for 20 h. After that time the reaction was cooled to rt, concentrated under reduced pressure, diluted with water (50 mL) and saturated NaHCO3 solution was added to adjust the pH to 8. The precipitated solids were collected by filtration, washed with water and dried. The product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol to 97:3 dichloromethane/methanol) to give 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.550 g, 49%) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 11.34 (s, 1H), 8.28-8.33 (m, 1H), 8.19-8.27 (m, 1H), 7.47 (dd, J=8.01, 1.76 Hz, 1H), 6.82 (d, J=2.34 Hz, 1H), 6.62 (d, J=2.34 Hz, 1H), 3.91 (s, 3H), 3.86 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ −68.08 (d, J=8.03 Hz); ESI MS m/z 302 [M+H]+.

後処理

  1. temperatureAfter that time the reaction was cooled to rt
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with water (50 mL) and saturated NaHCO3 solution
  4. additionwas added
  5. filtrationThe precipitated solids were collected by filtration
  6. washwashed with water
  7. customdried
  8. customThe product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol to 97:3 dichloromethane/methanol)

出典と根拠

ORDレコード
ord-9dbf94ea01ef4f5dbdb55341c899ff4d
出典データセット
uspto-grants-2016_03
特許番号
US09278940B2

反応ノート

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